While new FDA approval will enable personalized treatment of a genetic pathway that can cause obesity, a five-year study in nutrition for precision health funded by the NIH will open new opportunities for precision medicine programs
The market for companion diagnostics appears to be expanding beyond targeted therapies for oncology. A recent approval by the US Food and Drug Administration (FDA) has opened the door for clinical use of a precision medicine drug to combat obesity.
The treatment and the companion diagnostic test (CDx) address a rare genetic condition, called Bardet-Biedl Syndrome. This condition affects 4 in 1 million people, and while uncommon, Bardet-Biedl Syndrome affects multiple systems of the body. One of the hallmark signs of the condition is obesity that results from genetic variations that affect the chemicals influencing how someone feels full after eating.
“There is an important distinction between general obesity—a multifactorial condition influenced by multiple genes and environmental factors—and diseases of obesity caused by single-gene variants (monogenic),” according to a news release from Wisconsin-based PreventionGenetics LLC, the genetic testing laboratory and the subsidiary of Exact Sciences, in the company’s announcement. “Like many other genetic disorders, monogenic obesity is extremely rare, with a prevalence of less than 4% in individuals with early onset obesity.”
A distinguishing factor with the FDA approval, however, is that it is based on confirming specific variants or genes that are interpreted as pathogenic, likely pathogenic, or of uncertain significance (VUS). In addition, the CDx panel test approval comes nearly two years after the drug was first cleared by the FDA, receiving orphan disease designation, Breakthrough Therapy designation, and Priority Review, according to FDA news at that time.
Product of a Pharma Genetic Testing Lab Partnership
The FDA defines a companion diagnostic as a “medical device, often an in vitro device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product. The test helps a healthcare professional determine whether a particular therapeutic product’s benefits to patients will outweigh any potential serious side effects or risks.”
Because a companion diagnostic device is “essential for the safe and effective use” of the drug to which it has been assigned, it is identified on the drug’s product label.
The FDA recently granted De Novo marketing authorization to PreventionGenetics for its product called the POMC/PCSK1/LEPR CDx Panel, classified as a Setmelanotide Eligibility Gene Variant Detection System. FDA documents explain that this is a next generation sequencing (NGS)-based in vitro diagnostic test that analyzes genomic DNA isolated from blood or saliva.
The CDx panel test detects germline nucleotide substitutions, short insertions and deletions, and copy number variants (CNVs) within the following three genes:
• Pro-opiomelanocortin (POMC)
• Proprotein Convertase Subtilisin/Kexin type 1 (PCSK1)
• Leptin Receptor (LEPR)
Together, the FDA-cleared test and its target drug, Imcivree (setmelanotide), realize an earlier partnership between Rhythm Pharmaceuticals and the PreventionGenetics genetic testing laboratory, a lab that also offers no-cost sponsored testing programs for a variety of disease targets.
Now, with a new FDA supplemental indication approval of Imcivree as a treatment for weight management in patients with Bardet-Biedl Syndrome, combined with the FDA-approved POMC/PCSK1/LEPR companion diagnostic genetic test as a Class II medical device, we may see the drug used more broadly in the US.
Pathways to a Precision Medicine Programs
Like most precision medicine advances, Imcivree and its companion diagnostic test will benefit only a small portion of the overall population that it targets. The larger impact, however, is that it shows that precision medicine will be applied well beyond oncology.
With obesity linked to serious health problems in many parts of the world, it makes sense that obesity will develop into a niche precision medicine program. There is growing focus on nutrition as well.
Earlier this year, the National Institutes of Health (NIH) launched a five-year study called Nutrition for Precision Health. With it, the NIH announced $170 million in funding for clinics and centers across the country toward the development of algorithms that predict individual responses to food and dietary routines.
“Gaps persist in our understanding of digestion, absorption, distribution, metabolism, excretion, and storage of nutrients throughout the body,” states the 2020-2030 Strategic Plan for NIH Nutrition Research. “Despite extensive rigorous research, we still have incomplete knowledge about the molecular processes that drive these basic body functions. Expanded bioinformatic analyses of a wide range of nutrition-related genes and pathways will help to fill these gaps. One salient example is the large gene family that encodes membrane transporters for nutrients. Proteins encoded by these genes are clinically relevant as potential drug targets and transporters.”
According to the NIH, the objectives of the new precision nutrition study, specifically, are:
1. To examine individual differences observed in response to different diets by studying the interactions between diet, genes, proteins, microbiome, metabolism and other individual contextual factors;
2. To use artificial intelligence (AI) to develop algorithms to predict individual responses to foods and dietary patterns; and
3. To validate algorithms for clinical application.
The precision nutrition study has the goal of providing insights into how different individuals respond to different diets and enabling clinicians to predict individual dietary effects. The benefit is that precision nutrition will offer a personalized approach that can be applied to more than just a small subsegment of the population. We can expect to see new tools emerge.
As healthcare leaders recognize that obesity is a significant barrier to health and healing, and evidence-based nutrition and weight management programs are beneficial for the masses, new tools for the broader population could not only reduce health risk and improve outcomes, but lower healthcare costs.
PreventionGenetics Receives FDA Approval for its Companion Diagnostic Genetic Test as a Class II Medical Device
FDA approves treatment for weight management in patients with Bardet-Biedl Syndrome aged 6 or older
FDA Approves First Treatment for Weight Management for People With Certain Rare Genetic Conditions
FDA approvals: 2020 approval, 2022 supplemental indication approval, POMC/PCSK1/LEPR CDx Panel
2020–2030 Strategic Plan for NIH Nutrition Research A Report of the NIH Nutrition Research Task Force
Nutrition for Precision Health